The anti-tumour effect of CD8+ infiltration is associated with Human Leukocyte Antigen Class I expression and tumour proliferation in colorectal cancer

Purpose The host inflammatory response is an important determinant of cancer outcome, however, the factor/s that regulate this response remains unclear. We aimed to determine if Human Leukocyte Antigen (HLA) class I and tumour cell proliferation are associated with CD8 + infiltration and survival in patients undergoing potentially curative resection for colorectal cancer. Methods HLA class I expression (W6/32 and B2-microglobulin) and tumour proliferation index (Ki67) were quantified using immunohistochemistry on tissue micro arrays (TMA). The local inflammatory response at the invasive margin was assessed using the Klintrup-Makinen (K-M) score and CD8 + infiltration was assessed at the invasive margin (mCD8 + ), stroma (sCD8 + ) and cancer cell nests (cCD8 + ). Results Preserved HLA class I expression was associated with lower Dukes’ stage (p=0.032), lower T stage (p=0.040) and higher cCD8 + (p=0.003). High Ki67 was associated with a good K-M score (p<0.001), higher mCD8 + (p=0.033), higher sCD8 + (p=0.025) and higher cCD8 + (p<0.001). On binary logistical regression analysis both preserved HLA class I expression (HR 1.99 95%CI (1.13–3.51),p=0.012) and high Ki67 (HR 2.63 95%CI (1.08–6.38),p=0.033) were independently associated with higher CD8 + infiltration within the cancer cell nests. On multivariate survival analysis, preserved HLA class I expression was associated with disease free (HR 0.47 95%CI (0.25–0.89),p=0.020) and cancer specific survival (HR 0.52 95%CI (0.28–0.97),p=0.038). Conclusion This study suggests that a pronounced local inflammatory response is independently associated with both, HLA class I expression and tumour proliferation.